T lymphocytes play a critical role in host defense against microbes and cancer. A remarkable feature of the signals that trigger T cell participation in the immune response is that every cell appears to have a mandate that assures its daughters will not uniformly adopt the same fate. This proposal develops novel methodologies to image the characteristics of dividing T cells during the course of an infectious disease. The aims of the project are to test the importance of unequal cellular inheritance in the earliest stages of the immune response, where an abundance of cell fate decisions are being made (Aim 1), in the re-challenge response wherein memory T cells may be mimicking the regenerative behavior of adult stem cells (Aim 2), and in chronic infection because this scenario may tax the regenerative limits of normal memory T cells (Aim 3). The studies proposed herein should offer novel approaches for maintaining lifelong immunity against chronic infections and for eliminating many life-threatening infectious diseases.